Lennette J. Benjamin

Definitions of the phenotypic manifestations of sickle cell disease

Sickle cell disease (SCD) is a pleiotropic genetic disorder of hemoglobin that has profound multiorgan effects. The low prevalence of SCD (∼100,000/US) has limited progress in clinical, basic, and translational research. Lack of a large, readily accessible population for clinical studies has contributed to the absence of standard definitions and diagnostic criteria for the numerous complications of SCD and inadequate understanding of SCD pathophysiology. In 2005, the Comprehensive Sickle Cell Centers initiated a project to establish consensus definitions of the most frequently occurring complications. A group of clinicians and scientists with extensive expertise in research and treatment of SCD gathered to identify and categorize the most common complications. From this group, a formal writing team was formed that further reviewed the literature, sought specialist input, and produced definitions in a standard format. This article provides an overview of the process and describes 12 body system categories and the most prevalent or severe complications within these categories. A detailed Appendix provides standardized definitions for all complications identified within each system. This report proposes use of these definitions for studies of SCD complications, so future studies can be comparably robust and treatment efficacy measured. Use of these definitions will support greater accuracy in genotype–phenotype studies, thereby achieving a better understanding of SCD pathophysiology. This should nevertheless be viewed as a dynamic rather than final document; phenotype descriptions should be reevaluated and revised periodically to provide the most current standard definitions as etiologic factors are better understood, and new diagnostic options are developed. Am. J. Hematol. 2010.

Sickle cell-related pain: Perceptions of medical practitioners

Pain is the most common problem encountered by patients with sickle cell disease (SCD). We report the results of a survey sent to hematologists and emergency department (ED) physicians regarding their perceptions and practices concerning pain and its management. Hematologists and ED physicians differed considerably in their perceptions about the natural history of the pain, and about the percentage of patients who are addicted to analgesics. Fifty-three percent of the ED physicians and 23% of the hematologists thought that more than 20% of patients are addicted. These beliefs and perceptions about SCD-related pain and the prevalence of addiction must be addressed if clinical care is to be changed substantively.

Safety of Purified Poloxamer 188 in Sickle Cell Disease: Phase I Study of a Non‐ionic Surfactant in the Management of Acute Chest Syndrome

Acute chest syndrome (ACS) is the most common cause of death in patients with sickle cell anemia. Its management is primarily palliative. We performed a Phase I evaluation of purified poloxamer 188 (a non‐ionic surfactant) in the management of ACS. Forty‐three patients with sickle cell disease and ACS were treated with doses as high as 2960 mg/day by continuous intravenous (IV) infusion. The maximum tolerated dose has not been identified. No evidence of renal toxicity or other limiting adverse events were found. One adult patient died due to sepsis and adult respiratory distress syndrome, which were unrelated to treatment. Poloxamer 188 is safe to administer to patients with ACS, and preliminary data suggest that it may shorten its duration and the length of hospitalization in a dose related manner. Children appeared to benefit more than adults. The data and safety profile justify further studies with purified poloxamer 188 in the treatment of ACS.

Secretory Phospholipase A2 Levels in Patients with Sickle Cell Disease and Acute Chest Syndrome

In a multicenter study (eight centers), we determined secretory phospholipase A2 (sPLA2) levels in patients with sickle cell disease and acute chest syndrome (ACS). The diagnosis of ACS was made according to established criteria. The sPLA2 levels were determined in blood samples collected at baseline (time of diagnosis) and serially thereafter up to day 22–35 follow-up visits. Thirty-four of 43 (80%) patients with ACS had enzyme levels ≥1.00 AU at baseline. The enzyme levels decreased significantly on Days 2 through Days 25–35 after baseline. Nine of 43 (20%) patients had baseline sPLA2 values of <1.00 AU with six of them never exceeding 1.00 AU at any point in time during follow-up. The data indicate that the reliability of sPLA2 for predicting the development of ACS is not perfect (100%) as was previously reported but occurs in about 80% of the patients.